ABSTRACT Insufficient sleep is a rapidly growing public health problem that imposes an enormous socioeconomic burden on modern societies. More than 20% of adults do not get enough sleep, resulting in over $60 billion yearly costs primarily due to loss of productivity. Sleep plays a vital role across systems and processes, and is critical for maintaining organ health. Acute sleep loss impacts safety and impairs short-term cognitive and physical performance. Repeated insufficient sleep has profound long-term effects on overall health and increases the risk of morbidity, including diabetes, obesity and hypertension, and mortality. The adverse effects of acute sleep loss versus repeated sleep restriction on the physiological mechanisms that control cognitive and cardiovascular function remain elusive. It is unclear how insufficient sleep affects brain and heart electrodynamics and their coupling across temporal scales, whether both systems adapt to repeated sleep restriction and whether recovery sleep restores their dynamics to their normal baselines. Using a combination of novel signal processing and statistical methods and a unique dataset of continuous EEG and ECG signals, collected during a relatively large inpatient 21-day repeated sleep restriction and recovery study, this project will investigate these questions, with the ultimate goal to elucidate the dynamic responses of the brain and heart to the repeated stress of insufficient sleep. It is hypothesized that 1) single episodes of sleep loss and repeated sleep restriction have distinct effects on the brain and heart and their dynamic coupling, resulting in differential electrophysiological responses across time scales; 2) short-term recovery sleep following chronic insufficient sleep does not restore neural and cardiac dynamics to their normative values. Traditional analyses of physiological data from sleep studies use relatively simple computational approaches and typically focus on the sleep period. Data collected during wakefulness receive relatively little attention, despite a significant unmet need to elucidate the impact of insufficient sleep on neural and cardiovascular mechanisms supporting physical and cognitive performance during wakefulness. In Aim 1, advanced signal processing tools will be used to estimate multi-scale brain and heart dynamics from continuous EEG and ECG signals, collected from 43 neurologically healthy adults who were randomized to normal or restricted sleep (4 cycles, each including 3 nights of 4 h restricted sleep followed by 1 night of 8 h recovery sleep). In Aim 2, state-space and time-series models will be developed to estimate dynamic states of the brain and heart encoded in these signals and investigate their properties. Aim 3 will assess the causal coupling between the two systems and their dynamic states. Findings from this work may significantly improve our current knowledge of the dynamic responses of the brain and heart to acute sleep loss and repeated sleep restriction, and may significantly improve our understanding of the detrimental effects of these stressors on cognitive and cardiovascular health.